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Achondroplasia

Achondroplasia is a form of severe short stature, which can lead to a range of medical problems in children and adults.1,2

What is Achondroplasia?

Achondroplasia is the most common form of disproportionate short stature, affecting more than 250,000 people worldwide.1 It is a genetic condition caused by a change in the gene for fibroblast growth factor receptor 3 (FGFR3), which affects bone development.2 Achondroplasia has a significant impact on children’s growth, particularly at younger ages.3 Disproportionate growth between the bones and organs of people with achondroplasia can cause a number of orthopaedic (bone), neurological, respiratory, ear, nose, and throat (ENT), and dental issues.1

It is estimated that between 1 in 10,000 and 1 in 30,000 newborn babies has achondroplasia.2 Most of the time the condition results from a spontaneous change in the FGFR3 gene.2 It can also be inherited as an autosomal dominant trait, which means that if either parent has achondroplasia, each time they have a child there is a 50% chance of that child having the condition.4

Diagnosing Achondroplasia4,5

The characteristics of achondroplasia are distinctive, and the condition may be suspected during ultrasound scans in pregnancy and/or through clinical and radiological features at birth. The diagnosis can be confirmed by genetic testing.

Medical Complications in Achondroplasia

Most children and adults with achondroplasia enjoy good general health, but numerous complications can occur.5 These tend to appear at predictable ages throughout life.2 Problems that can arise in infants and children include spinal cord compression, recurrent ear infections (which can lead to loss of hearing), dental issues, and cardiorespiratory and sleep dysfunction such as sleep apnoea.2 Bowed legs can begin in childhood and affect more than 40% of adults.2 Many adults also experience complications due to stenosis (narrowing) around the spinal cord.2 Mortality is increased from birth to four years of age, and in the fourth and fifth decades of life.6

Managing the Complications of Achondroplasia

The complex array of medical issues that can be experienced by people with achondroplasia are best managed by a multidisciplinary team.1 Because known complications occur at different ages, they can be anticipated and tested for.2 Early monitoring and careful medical and surgical interventions are important for reducing rates of morbidity and mortality.1 Some of the complications of achondroplasia can result in the need for invasive surgeries such as spinal cord decompression and straightening of bowed legs.1,2 About a third of people with achondroplasia require surgery for symptomatic spinal stenosis, and 5-10% undergo cervical medullary (neck) decompression surgery.2 In some countries, limb-lengthening surgery is carried out on children with achondroplasia, but can be associated with a potentially high rate of complications.7-9


References
  1. Ireland P et al. Optimal management of complications associated with achondroplasia. Appl Clin Genet 2014;7:117-25.
  2. Horton WA et al. Achondroplasia. Lancet 2007;370:162-72.
  3. Merker A et al. Growth in achondroplasia: Development of height, weight, head circumference, and body mass index in a European cohort. Am J Med Genet Part A 2018;1-12.
  4. Hoover-Fong J et al, AAP Committee on Genetics. Health supervision for people with achondroplasia. Pediatrics 2020;145(6):e20201010.
  5. Unger S et al. Current care and investigational therapies in achondroplasia. Curr Osteoporos Rep 2017;15:53-60.
  6. Savarirayan R et al. C-type natriuretic peptide analogue therapy in children with achondroplasia. N Engl J Med 2019;381(1):25-35.
  7. Donaldson J et al. Achondroplasia and limb lengthening: Results in a UK cohort and review of the literature. J Orthop 2015;12(1):31-34.
  8. Leiva-Gea A et al. Staged upper and lower limb lengthening performing bilateral simultaneous surgery of the femur and tibia in achondroplastic patients. Arch Orthop Trauma Surg 2020;140(11):1665-76.
  9. Schiedel F and Rödl R. Lower limb lengthening in patients with disproportionate short stature with achondroplasia: a systematic review of the last 20 years. Disabil Rehabil 2012;34(12):982-87.